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Ocular manifestations of central insulin resistance

Neural Regeneration Research 2023年第5期18卷 1139-1146页

作者： Muneeb A.Faiq Trina Sengupta Madhu Nath Thirumurthy Velpandian Daman Saluja rima dada Tanuj dada Kevin C.Chan Dr.Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical SciencesNew DelhiIndia Neuroimaging and Visual Science Laboratory Department of OphthalmologyNYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Medical Biotechnology Laboratory Dr.B.R.Ambedkar Center for Biomedical ResearchUniversity of DelhiDelhiIndia Dr.Baldev Singh Sleep Laboratory Department of PhysiologyAll India Institute of Medical SciencesNew DelhiIndia Department of Ocular Pharmacology Dr.Rajendra Prasad Center for Ophthalmic SciencesAll India Institute of Medical SciencesNew DelhiIndia Laboratory for Molecular Reproduction and Genetics Department of AnatomyAll India Institute of Medical SciencesNew DelhiIndia

Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most s

关键词： brain ciliary bodies gene expression inflammation insulin receptor insulin resistance intraocular pressure neurodegeneration optic nerve retina retinal ganglion cells trabecular meshwork

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AZF microdeletions associated with idiopathic and non idiopathic cases with cryptorchidism and varicocele

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Asian Journal of Andrology 2002年第4期4卷 259-263页

作者： rima dada N.P. Gupta K. Kucheria Department of Anatomy Department of Urology All India Institute of Medical Sciences New Delhi-110029 IndiaDepartment of Anatomy

AIM: To identify submicroscopic interstitial deletions in azoospermia factor (AZF) loci in idiopathic and non-idiopathic cases of male infertility in Indians. METHODS: One hundred and twenty two infertile males with oligozoospermia or azoospermia were included in this study. Semen analysis was done to determine the sperm density, i.e., normospermia (>20 million/mL), oligozoospermia (

关键词： azoospermia factor oligozoospermia azoospermia infertility

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Mild oxidative stress is beneficial for sperm telomere length maintenance

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World Journal of Methodology 2016年第2期6卷 163-170页

作者： Swetasmita Mishra Rajeev Kumar Neena Malhotra Neeta Singh rima dada Laboratory for Molecular Reproduction and Genetics Department of Anatomy All India Institute of Medical Sciences Department of Urology All India Institute of Medical Sciences Department of Obstetrics and Gynaecology All India Institute of Medical Sciences

AIM:To evaluate telomere length in sperm DNA and its correlation with oxidative stress(normal,mild,severe).METHODS:The study included infertile men(n=112)and age matched fertile controls(n=102).The average telomere length from the sperm DNA was measured using a quantitative real time PCR based *** reactive oxygen species(ROS)and 8-Isoprostane(8-IP)levels were measured by chemiluminescence assay and ELISA ***:Average sperm telomere length in infertile men and controls was 0.609±0.15 and 0.789±0.060,respectively(P35 RLU/s/million sperm)average telomere length was decreased to 0.595±***:Mild oxidative stress results in lengthening of telomere length,but severe oxidative stress results in shorter *** telomere maintenance is a complex trait,the study shows that mild oxidative stress is beneficial in telomere length maintenance and thus a delicate balance needs to be established to maximize the beneficial effects of free radicals and prevent harmful effects of supra physiological *** molecular evaluation of telomere structure,its correlation with oxidative stress would aid in elucidating the cause of accelerated telomere length attrition.

关键词： Telomere Oxidative stress Reactive oxygen species Infertility 8-Isoprostane

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Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome

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Asian Journal of Andrology 2006年第1期8卷 81-88页

作者： Anurag Mitra rima dada Rajeev Kumar Narmada Prasad Gupta Kiran Kucheria Satish Kumar Gupta Gamete Antigen Laboratory National Institute of ImmunologyAruna Asaf Ali MargNew Delhi 110067India Department of Anatomy Department of Urology All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India

Aim： To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter＇s syndrome （KFS）. Methods： Blood and semen samples were collected from azoospermic patients with KFS （n = 14） and a control group of men of proven fertility （n = 13）. Semen analysis was done according to World Health Organization （WHO） guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization （FISH） and measurement of plasma follicle stimulating hormone （FSH） by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction （PCR） of 16 sequence tagged sites （STS） and three genes （DFFRY, XKRY and RBM1 Y） was performed on isolated genomic DNA. Testicular fine needle aspiration cytology （FNAC） was done in selected cases. Results： Y chromosome microdeletions spanning the azoospermia factor （AZF）a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion： Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques. （Asian JAndrol 2006 Jan; 8： 81-88）

关键词： azoospermia azoospermia factor follicle stimulating hormone Klinefelter's syndrome Y chromosome microdeletion

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Implications of Cytogenetic Abnormalities and Azoospermia Factor Microdeletions in Assisted Procreation

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Journal of Reproduction and Contraception 2007年第3期18卷 231-235页

作者： rima dada R Kumar M Bilal Shamsi Sarabpreet Singh Col R K Sharma A Varshney Laboratory of Molecular Reproduction and Genetics Department of AnatomyAIIMS N Delhi 110029 India Anatomy Department AIIMSN Delhi 110029 India ART centre Obstretics and Gynaecology Department Army Research and Referral hospitalNew Delhi India AIIMS N Delhi 110029 India

Assisted procreation techniques have revolutionized the management of infertility and have offered hope to millions of infertile couples. The main aim of these procedures is to produce healthy offspring. However recent studies on short term outcome of ART have reported a higher incidence of low birth weight, development delay, imprinting defects, sex and autosomal structural abnormalities, major and minor congenital malformation and certain cancers in babies conceived via ART. Further the health of ART conceived children beyond the neonatal period have been less well evaluated. A large number of infertile couples opting for ART have an underlying genetic aetiology. These genetic aberrations are iatrogenitically transmitted via ART. Thus it is important that all couples undergo a detailed and comprehensive genetic evaluation prior to ART.

关键词： genetics chromosomal abnormality AZF Yq microdeletion assisted reproduction ART

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Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood

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Asian Journal of Andrology 2007年第5期9卷 720-722页

作者： rima dada Rakesh Kumar M. B. Shamsi Rajeev Kumar Kiran Kucheria Raj K. Sharma Satish K. Gupta Narmada P. Gupta Laboratory for Molecular Reproduction and Genetics Anatomy DepartmentAll India Institute of Medical Sciences New Delhi 29 India Urology Department All India Institute of Medical Sciences New Delhi 29 India Endocrinology Department All India Institute of Medical Sciences New Delhi 29 India ART Centre Army Research and Referral Hospital New Delhi 57 India Gamete Antigen Laboratory National Institute of Immunology New Delhi 67 India

Aim： To determine if Yq microdeletion frequency and loci of deletion are similar in two tissues （blood and sperm） of different embryological origin. Methods： The present study included 52 infertile oligozoospermic cases. In each case, DNA was isolated from blood and sperms and polymerase chain reaction （PCR） microdeletion analysis was done from genomic DNA isolated from both the tissues. The PCR products were analyzed on a 1.8% agarose gel. PCR amplifications found to be negative were repeated at least three times to confirm the deletion of a given marker. Results： Only 1 case harbored microdeletion in blood DNA, whereas 4 cases harbored microdeletion in sperm DNA. Conclusion： The frequency of Yq microdeletions is higher in germ cells as compared to blood. As the majority of infertile couples opt for assisted reproduction procreation techniques （ART）, Yq microdeletion screening from germ cells is important to understand the genetic basis of infertility, to provide comprehensive counseling and most adapted therapeutics to the infertile couple.

关键词： assisted reproductive techniques infertility semen genomic DNA Yq screening

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